Diabetes Res Clin Pract. 2026 Jan 25:113104. doi: 10.1016/j.diabres.2026.113104. Online ahead of print.
ABSTRACT
AIMS: This study examines the incidence of anxiety, depression, and suicidality after treatment initiation with antihyperglycemic mediations in patients with type 2 diabetes (T2D) which take metformin as first-line treatment.
METHODS: A large cohort study was conducted using TriNetX electronic health records andincluded adults (≥18 years) with T2D who used metformin and initiated GLP-1 RAs, SGLT2i, DPP4i, or SU between 1 April 2013 and 31 December 2019.
RESULTS: Among 100,500 patients, 16,424 started using GLP-1 RAs, 13,855 SGLT2i, 27,614 DPP4i, and 42,607 SU. In a median follow-up of 5.5 years, GLP-1 RAs were associated with a higher risk of depression compared to SGLT2i (HR 1.19, 95% CI 1.11-1.28), and DPP4i (HR 1.06, 95% CI 1.00-1.13) but not SU. Anxiety disorder risk was also higher for GLP-1 RAs versus SGLT2i (HR 1.09, 95% CI 1.02- 1.16) and DPP4i (HR 1.07, 95% CI 1.02-1.13) but not SU. On the contrary, GLP-1 RAs were associated with a lower risk for suicidal ideation in comparison with SU (HR 0.62, 95% CI 0.44-0.87).
CONCLUSIONS: GLP-1 RAs are associated with higher risk of anxiety and depression but no difference in suicidality and self-harm in comparison to SGLT2i, DPP4i, and lower suicidality risk compared to SU.
PMID:41592697 | DOI:10.1016/j.diabres.2026.113104
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